The present invention relates to permselective membranes and to methods for their production. Specifically, it relates to permselective membranes which, when used for blood treatment, maintain a high hemofiltration rate and a low albumin permeability for a long period of time through control of the molecular weight distribution of the hydrophilic polymer in the membrane, and which are high in permselectivity to uremic toxins including medium-to-high molecular weight proteins, and also relates to methods for their production.
Natural materials such as cellulose and synthetic polymer membrane materials such as polysulfone, polymethylmethacrylate (PMMA) and polyacrylonitrile have been widely used in semipermeable membranes for blood treatment, and various studies have been made in an attempt to develop dialysis techniques which function similarly to the human kidney in performing blood treatment for patients with chronic renal failure. Of these membranes, much attention has recently been focused on polysulfone as it is sufficiently high in permeability to meet the latest improved dialysis techniques. Conventionally, polysulfone has been widely used as heat-resistant, thermoplastic engineering plastics material in the fields of automobiles, electric appliances, and medical devices. A semipermeable membrane made of polysulfone alone, however, is too high in intermolecular cohesive strength and low in affinity with blood because of its hydrophobic nature, and therefore cannot be applied to blood treatment. To solve this problem, a method was proposed wherein pores were produced by adding and subsequently leaching such pore-forming additives as hydrophilic polymers and inorganic salts while simultaneously forming a hydrophilic surface over the polymer material to provide a semipermeable membrane or a reverse osmosis membrane. Since then, a variety of published patent applications have appeared. Such methods for producing semipermeable membranes for blood treatment include those listed below:
a method wherein a metal salt is added in forming a membrane;
a method wherein a hydrophilic polymer is added in forming a membrane; and
a method wherein a polyhydric alcohol is added in forming a membrane.
In the case of JP-A-61-232860 and JP-A-58-114702, where a polyhydric alcohol such as polyethylene glycol is added in forming a membrane, however, insufficient rinsing leaves residual alcohol in the membrane, which may cause trouble in the eyes of patients during dialysis. In the case of JP-B-06-075667, a membrane formation method which uses polyvinyl pyrrolidone is disclosed, but the resultant membrane, though high in water permeation performance, is too high in albumin permeability for use in blood treatment (dialysis). A similar problem can occur in the case of JP-A-62-121608 where a metal salt is used. JP-A-6-233921 proposes a hollow yarn membrane production method in which a high molecular weight hydrophilic polymer is added to increase the viscosity so that a good solvent for the solution can be used as total core liquid. This method, however, cannot control the albumin permeability of the membrane. Furthermore, no description is given concerning the diffusing performance of the resultant hollow yarn membrane, and no information is provided on the molecular weight distribution of the hydrophilic polymer in the membrane. By the method disclosed in JP-B-02-018695, a membrane that is high in stain resistance and easy to clean can be produced by adding high molecular weight polyvinyl pyrrolidone up to a high content relative to polysulfone to allow large amounts of polyvinyl pyrrolidone to remain in the membrane, though such a high diffusing performance as sought in the present invention cannot be achieved. Moreover, JP-B-05-054373 discloses a membrane which is produced by starting with a low-viscosity solution consisting of polysulfone and relatively low molecular weight polyvinyl pyrrolidone and ending with washing for nearly complete removal of the polyvinyl pyrrolidone. However, there is no reference to a high diffusing performance associated with the molecular weight distribution of the hydrophilic polymer remaining in the membrane. As more than 20 years has passed since the advent of dialysis, many complications caused by long-term dialysis have been reported, especially recently, and attention is now focused on proteins with molecular weights of 20,000 to 40,000 as causative agents of the carpal canal syndrome and other dialysis syndromes. None of the above patent publications, however, has disclosed a hollow yarn membrane that can play or imitate the role of the human kidney in positively removing such proteins as listed above.
After earnest studies aiming to solve the above problems, we found a permselective membrane, in accordance with the invention, which allows dialysis to be carried out during which the membrane minimizes the permeability to albumin, a useful protein, while at the same time maintaining a high water permeability, and efficiently removing medium-to-high molecular weight uremia-causing proteins. We also found a method for production of such a membrane.